Anti-Hepatitis B Virus Activity and Mechanisms of Recombinant Human Serum Albumin-Interferon-α-2b Fusion Protein in vitro and in vivo

作者：Xu Bingfa; Fan Qinglin; Huang Hui; Wang Canjun; Wei Wei; Song Lihua^*

来源：Pharmacology, 2009, 83(6): 323-332.

DOI：10.1159/000215588

• Recombinant human serum albumin-interferon-alpha-2b fusion protein
• Hepatitis B virus
• Duck hepatitis B virus
• HepG2 2.2.15
• 2 ',5 '-Oligoadenylate synthetase

Aims: To evaluate the anti-hepatitis B virus (anti-HBV) effects and mechanisms of recombinant human serum albumin-interferon-alpha-2b fusion protein (rHSA-IFN alpha-2b) in vitro and in vivo. Methods: The inhibiting effects on HBV replication were examined in the HepG2 2.2.15 cell line and in ducks, and the expressions of signal transducers and transactivator 1 (STAT1), IFN-stimulated gene factor 3 (ISGF3) and 2',5'-oligoadenylate synthetase 1 (OAS1) were investigated by the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Results: In vitro, at concentrations from 0.075 to 1.2 nmol/l, rHSA-IFN alpha-2b inhibited the releases of extracellular hepatitis B surface antigen, hepatitis B e antigen and HBV DNA in a dose-dependent manner; rHSA-IFN alpha-2b also increased the levels of STAT1, ISGF3 and OAS1. In vivo, rHSA-IFN alpha-2b reduced the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin and duck hepatitis B virus (DHBV) DNA in the sera of DHBV-infected ducks. Conclusions: We provide the first evidence that rHSA-IFN alpha-2b significantly inhibits HBV replication in HepG2 2.2.15 cells and in ducks, and that the antiviral effect of rHSA-IFN alpha-2b in vivo is more potent than that of IFN alpha-2b. The anti-HBV mechanism probably operates by triggering the JAK-STAT signaling pathway and increasing the expression of OAS1.

• 出版日期2009
• 单位安徽医科大学